Lithium has an important role in the management of a number of psychiatric disorders. Lithium is administered orally in the form of tablets, capsules, or liquid. Because lithium has the potential for having adverse effects on the kidneys and thyroid, it is important to carefully control the lithium dosage. Heretofore, the blood (serum) lithium level has been monitored through time-consuming and expensive procedures of flame photometry or atomic absorption spectrophotometry (See Toxicology and Therapeutic Drug Monitoring, Chap. 61, "Lithium" pp. 1377-1379.)
Alternatives to these methods of analysis are presently under investigation. Lithium ion-selective electrodes have been proposed to monitor whole blood during lithium therapy wherein a lipophilic diamide is utilized as a neutral carrier (Zhukor et al. "Analytica Chimica Acta,"131 (1981) 117-122). Macrocyclic polyethers have been used to extract various alkali metal ions, including lithium (K. Ueno and M. Takagi, "Studies in Physical and Theoretical Chemistry," Vol. 27, pp. 279-293 (1983)); and lithium ion-selective fluorescent emission with synthetic macrocyclic ligands, particularly crowned azophenols, is reported by Tanigawa et al. in Tetrahedron Letters, Vol. 25, No. 46, pp. 5327-5330 (1984).
U.S. Patent No. 4,556,068 describes a method for determining the amount of lithium in the brain and kidneys wherein a particular portion of the body is irradiated with neutrons, producing tritium atoms and hydrogen gas, which can then be measured from a patient's breath, indicating quantities of lithium in the part of the body examined.
However, what is needed in the art is an efficient, unobtrusive, highly selective mode of analysis for lithium content. Such a device and indicator system would aid the clinician in the rapid and inexpensive control of lithium dosage, to provide a dosage regime that is likely to be therapeutic without running the risk of toxicity. The present invention provides just such an indicator and analysis system through the use of a composition containing a precursor to an arylmethane dye. Arylmethane dyes have been known since the 1800's (see K. Venkatarman, The Chemistry of Synthetic Dyes, Vol. II, Academic Press, N.Y., 1952, pp. 705 ff.). However, uses of these dyes have typically centered around their colored nature and thus, the dye compounds have been used as coloring agents and colorants, biological stains and the like. By contrast, the colorless precursors of the dyes have not found such application. Humphries, et al. in Biochem. and Biophys. Res. Comm. 50, 2 (1973) report the use of 4,4'-Bis-dimethylaminophenylcarbinol as a reagent for sulfhydryl and cysteine residues. However, the species that interacts with these residues is not actually the precursor carbinol form of the compound, but rather the colored resonance forms of the compound. Thus, the carbinol form must be first converted to the resonance forms to interact with these residues.